Thymosin alpha 1 modulates the expression of high affinity interleukin-2 receptors on normal human lymphocytes.
In this report we demonstrate that thymosin alpha 1 (T alpha 1), a synthetic peptide composed of 28 amino acid residues, and thymosin fraction 5 (TF5) enhance the number of high affinity interleukin 2 receptors (IL-2R) expressed by human peripheral blood lymphocytes in response to in vitro stimulation with phytohemagglutinin (PHA). Thymosins did not, however, alter the affinity of the IL-2R for its ligand. Dose-response studies using a wide range of concentrations indicated a bimodal distribution of responsiveness to T alpha 1. In most experiments the high and low concentration peaks of activity were observed at 10(-8) M and 10(-12) M, respectively, although peak responses were observed at different T alpha 1 concentrations in different donors. No effects were elicited by thymosins in the absence of mitogenic stimulation. Thymosin enhancement of PHA-induced high affinity IL-2R expression directly correlated with increased levels of Tac antigen expression, as determined by flow cytometry, and enhanced interleukin 2 (IL-2) production. Since the biological effects of IL-2 are associated with the occupancy of high affinity IL-2R, the findings presented in this report strongly suggest that thymosins play a significant role in the regulation of immune responses through the modulation of high affinity IL-2R expression.
Leichtling
K D
KD
Department of Medicine, George Washington University School of Medicine, Washington, DC 20037.
Serrate
S A
SA
Sztein
M B
MB
D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007202:Indicators and Reagents; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D011869:Radioligand Assay; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism*; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology
D007202:Indicators and Reagents; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D013947:Thymosin; D000077596:Thymalfasin